EP1500124B1 - Mass spectrometer - Google Patents
Mass spectrometer Download PDFInfo
- Publication number
- EP1500124B1 EP1500124B1 EP03708888A EP03708888A EP1500124B1 EP 1500124 B1 EP1500124 B1 EP 1500124B1 EP 03708888 A EP03708888 A EP 03708888A EP 03708888 A EP03708888 A EP 03708888A EP 1500124 B1 EP1500124 B1 EP 1500124B1
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- EP
- European Patent Office
- Prior art keywords
- ion
- gas
- capillary
- target
- conduit
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
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Images
Classifications
-
- H—ELECTRICITY
- H01—ELECTRIC ELEMENTS
- H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
- H01J49/00—Particle spectrometers or separator tubes
- H01J49/02—Details
- H01J49/10—Ion sources; Ion guns
- H01J49/16—Ion sources; Ion guns using surface ionisation, e.g. field-, thermionic- or photo-emission
- H01J49/161—Ion sources; Ion guns using surface ionisation, e.g. field-, thermionic- or photo-emission using photoionisation, e.g. by laser
- H01J49/164—Laser desorption/ionisation, e.g. matrix-assisted laser desorption/ionisation [MALDI]
-
- H—ELECTRICITY
- H01—ELECTRIC ELEMENTS
- H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
- H01J49/00—Particle spectrometers or separator tubes
- H01J49/02—Details
- H01J49/04—Arrangements for introducing or extracting samples to be analysed, e.g. vacuum locks; Arrangements for external adjustment of electron- or ion-optical components
- H01J49/0409—Sample holders or containers
- H01J49/0418—Sample holders or containers for laser desorption, e.g. matrix-assisted laser desorption/ionisation [MALDI] plates or surface enhanced laser desorption/ionisation [SELDI] plates
-
- H—ELECTRICITY
- H01—ELECTRIC ELEMENTS
- H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
- H01J49/00—Particle spectrometers or separator tubes
- H01J49/02—Details
- H01J49/04—Arrangements for introducing or extracting samples to be analysed, e.g. vacuum locks; Arrangements for external adjustment of electron- or ion-optical components
- H01J49/0468—Arrangements for introducing or extracting samples to be analysed, e.g. vacuum locks; Arrangements for external adjustment of electron- or ion-optical components with means for heating or cooling the sample
- H01J49/0477—Arrangements for introducing or extracting samples to be analysed, e.g. vacuum locks; Arrangements for external adjustment of electron- or ion-optical components with means for heating or cooling the sample using a hot fluid
Definitions
- the invention relates generally to the field of mass spectrometry and more particularly toward a heated target support to provide enhanced analtye ions in an atmospheric pressure matrix assisted laser desorption/ionization (AP-MALDI mass spectrometer.
- AP-MALDI mass spectrometer atmospheric pressure matrix assisted laser desorption/ionization
- the techniques have also had success on a broad based level of compounds including peptides, proteins, carbohydrates, oligosaccharides, natural products, cationic drugs, organoarsenic compounds, cyclic glucans, taxol, taxol derivatives, metalloporphyrins, porphyrins, kerogens, cyclic siloxanes, aromatic polyester dendrimers, oligodeoxynucleotides, polyaromatic hydrocarbons, polymers and lipids.
- compounds including peptides, proteins, carbohydrates, oligosaccharides, natural products, cationic drugs, organoarsenic compounds, cyclic glucans, taxol, taxol derivatives, metalloporphyrins, porphyrins, kerogens, cyclic siloxanes, aromatic polyester dendrimers, oligodeoxynucleotides, polyaromatic hydrocarbons, polymers and lipids.
- the analyte and matrix in solution is applied to a probe or target substrate.
- the solvent evaporates, the analyte and matrix co-precipitate out of solution to form a solid solution of the analyte in the matrix on the target substrate.
- the co-precipitate is then irradiated with a short laser pulse inducing the accumulation of a large amount of energy in the co-precipitate through electronic excitation or molecular vibration of the matrix molecules.
- the matrix dissipates the energy by desorption, carrying along the analyte into the gaseous phase. During this desorption process, ions are formed by charge transfer between the photo-excited matrix and analyte.
- the MALDI technique of ionization is performed using a time-of-flight analyzer, although other mass analyzers such as an ion trap, an ion cyclotron resonance mass spectrometer and quadrupole time-of-flight are also used. These analyzers, however, must operate under high vacuum, which among other things may limit the target throughput, reduce resolution, capture efficiency, and make testing targets more difficult and expensive to perform.
- AP-MALDI a technique referred to as AP-MALDI.
- This technique employs the MALDI technique of ionization, but at atmospheric pressure.
- the MALDI and the AP-MALDI ionization techniques have much in common. For instance, both techniques are based on the process of pulsed laser beam desorption/ionization of a solid-state target material resulting in production of gas phase analyte molecular ions.
- AP-MALDI can provide detection of a molecular mass up to 10 6 Da from a target size in the attamole range.
- levels of sensitivity become increasingly important.
- Various structural and instrument changes have been made to MALDI mass spectrometers in an effort to improve sensitivity. Additions of parts and components, however, provides for increased instrument cost.
- attempts have been made to improve sensitivity by altering the analyte matrix mixed with the target.
- US 4,968,885 A discloses methods and apparatus for liquid sample introduction into chemical detectors that require the sample to be transformed from a flowing stream into either gaseous or particulate states.
- the effluent from either a process stream or a liquid chromatograph is nebulized by combined thermal and penumatic processes within an inner fused silicon capillary tube heated by conduction through a relatively conductive sheathing gas from a surrounding electrical resistance heated outer capillary tube composed of a pure metal having a comparatively high linear relationship between temperature and electrical resistance to provide a uniform conduction of heat energy to the inner tube to form a well-collimated, partially or completely desolvated aerosol, with the less volatile solute components of the sample stream remaining in the particulate state.
- WO 00/77822 A2 discloses a mass spectrometer instrument for determining the molecular weight of labile molecules of biological importance.
- the instrument includes a MALDI ion source that is enclosed in a chamber with an inlet for admitting a gas and an ion sampling aperture for limiting gas flow from the chamber.
- US 6,140,639 A describes a system and a method for on-line coupling of liquid capillary separation with matrix-assisted laser desorption ionization mass spectrometric analysis.
- Analyte from liquid capillary separation is mixed with matrix molecules for matrix-assisted laser desorption ionization.
- Continuous flow of the analyte/matrix combined with vacuum conditions allows evaporation and crystallization of homogeneous samples on a solid sample surface. Dual use of laser irradiation to desorb/ionize and remove excess sample facilitates on-line use and automation.
- EP 0 964 427 A2 describes a mass spectrometer having a matrix-assisted laser desorption ionization (MALDI) source which operates at ambient pressure.
- the apparatus includes an ionization enclosure including a passageway configured for delivery of ions to the mass analysis device; means to maintain said ionization enclosure at an ambient pressure; a holder configured for maintaining a matrix containing said sample in the ionization enclosure; a source of laser energy, and means for directing at least a portion of the at least one ionized analyte into the passageway.
- MALDI matrix-assisted laser desorption ionization
- WO 03/073461 A1 is a prior art document according to Art. 54(3) EPC and describes an apparatus and method for use with a mass spectrometer.
- the ion enhancement system directs a heated gas toward ions produced by a matrix based ion source and detected by a detector.
- the ion enhancement system is interposed between the ion source and the detector.
- the analyte ions that contact the heated gas are enhanced and an increased number of ions are more easily detected by a detector.
- adjacent means, near, next to or adjoining. Something adjacent may also be in contact with another component, surround the other component, be spaced from the other component or contain a portion of the other component. For instance, a capillary that is adjacent to a conduit may be spaced next to the conduit, may contact the conduit, may surround or be surrounded by the conduit, may contain the conduit or be contained by the conduit, may adjoin the conduit or may be near the conduit.
- conduit refers to any sleeve, transport device, dispenser, nozzle, hose, pipe, plate, pipette, port, connector, tube, coupling, container, housing, structure or apparatus that may be used to direct a heated gas or gas flow toward a defined region in space such as an ionization region.
- the "conduit” may be designed to enclose a capillary or portion of a capillary that receives analyte ions from an ion source.
- the term should be interpreted broadly, however, to also include any device, or apparatus that may be oriented toward the ionization region and which can provide a heated gas flow toward or into ions in the gas phase and/or in the ionization region.
- the term could also include a concave or convex plate with an aperture that directs a gas flow toward the ionization region.
- the term "enhance” refers to any external physical stimulus such as heat, energy, light, or temperature change, etc.. that makes a substance more easily characterized or identified.
- a heated gas may be applied to "enhance” ions.
- the ions increase their kinetic energy, potentials or motions and are declustered or vaporized. Ions in this state are more easily detected by a mass analyzer. It should be noted that when the ions are "enhanced", the number of ions detected is enhanced since a higher number of analyte ions are sampled through a collecting capillary and carried to a mass analyzer or detector.
- Ion source refers to any source that produces analyte ions. Ion sources may include other sources besides AP-MALDI ion sources such as electron impact (herein after referred to as EI), chemical ionization (CI) and other ion sources known in the art.
- EI electron impact
- CI chemical ionization
- the term “ion source” refers to the laser, target substrate, and target to be ionized on the target substrate.
- the target substrate in AP-MALDI may include a grid for target deposition. Spacing between targets on such grids is around 1-10 mm. Approximately 0.5 to 2 microliters is deposited on each site on the grid.
- the term "ionization region" refers to the area between the ion source and the collecting capillary.
- the term refers to the analyte ions produced by the ion source that reside in that region and which have not yet been channeled into the collecting capillary.
- This term should be interpreted broadly to include ions in, on, about or around the target support as well as ions in the heated gas phase above and around the target support and collecting capillary.
- the ionization region in AP MALDI is around 1-5 mm in distance from the ion source (target substrate) to a collecting capillary (or a volume of 1-5 mm 3 ).
- the distance from the target substrate to the conduit is important to allow ample gas to flow from the conduit toward the target and target substrate. For instance, if the conduit is too close to the target or target substrate, then arcing takes place when voltage is applied. If the distance is too far, then there is no efficient ion collection.
- an "ion enhancement system” refers to any device, apparatus or components used to enhance analyte ions. The term does not include directly heating a capillary to provide conductive heat to an ion stream.
- an "ion enhancement system” comprises a conduit and a gas source.
- An ion enhancement system may also include other devices well known in the art such as a laser, infrared red device, ultraviolet source or other similar type devices that may apply heat or energy to ions released into the ionization region or in the gas phase.
- ion production and enhancement system refers to any device, apparatus or components used to produce and enhance analyte ions.
- a heated target support can be used to both provide for ion production and enhancement.
- the term does not include directly heating a capillary to provide conductive heat to an ion stream.
- the ion production and enhancement system may further comprise an ion source and an ion enhancement system.
- the ion source and the ion enhancement system can be separate devices or integrated, part of or comprise the same apparatus.
- ion transport system refers to any device, apparatus, machine, component, capillary, that shall aid in the transport, movement, or distribution of analyte ions from one position to another.
- the term is broad based to include ion optics, skimmers, capillaries, conducting elements and conduits.
- matrix based refers to an ion source or mass spectrometer that does not require the use of a drying gas, curtain gas, or desolvation step. For instance, some systems require the use of such gases to remove solvent or cosolvent that is mixed with the analyte. These systems often use volatile liquids to help form smaller droplets. The above term applies to both nonvolatile liquids and solid materials in which the sample is dissolved. The term includes the use of a cosolvent. Cosolvents may be volatile or nonvolatile, but must not render the final matrix material capable of evaporating in vacuum.
- Such materials would include, and not be limited to m-nitrobenzyl alcohol (NBA), glycerol, triethanolamine (TEA), 2,4-dipentylphenol,1,5-dithiothrietol/dierythritol (magic bullet), 2-nitrophenyl octyl ether (NPOE), thioglycerol, nicotinic acid, cinnamic acid, 2,5-dihydroxy benzoic acid (DHB), 3,5-dimethoxy-4-hydroxycinnamic acid (sinpinic acid), ⁇ -cyano-4-hydroxycinnamic acid (CCA), 3-methoxy-4-hydroxycinnamic acid (ferulic acid),), monothioglycerol, carbowax, 2-(4-hydroxyphenylazo)benzoic acid (HABA), 3,4-dihydroxycinnamic acid (caffeic acid), 2-amino-4-methyl-5-nitropyridine with their cosolvents and derivatives.
- gas flow refers to any gas that is directed in a defined direction in a mass spectrometer.
- the term should be construed broadly to include monatomic, diatomic, triatomic and polyatomic molecules that can be passed or blown through a conduit.
- the term should also be construed broadly to include mixtures, impure mixtures, or contaminants.
- the term includes both inert and non-inert matter. Common gases used with the present invention could include and not be limited to ammonia, carbon dioxide, helium, fluorine, argon, xenon, nitrogen, air etc..
- gas source refers to any apparatus, machine, conduit, or device that produces a desired gas or gas flow. Gas sources often produce regulated gas flow, but this is not required.
- capillary or “collecting capillary” shall be synonymous and will conform with the common definition(s) in the art.
- the term should be construed broadly to include any device, apparatus, orifice, tube, hose or conduit that may receive ions.
- detector refers to any device, apparatus, machine, component, or system that can detect an ion. Detectors may or may not include hardware and software. In a mass spectrometer the common detector includes and/or is coupled to a mass analyzer.
- the ion source 3 may be located in a number of positions or locations.
- a variety of ion sources may be used with the present invention.
- EI, CI or other ion sources well known in the art may be used with the invention.
- the ion enhancement system 2 may comprise a conduit 9 and a gas source 7. Further details of the ion enhancement system 2 are provided in FIGS 2-3 .
- the ion enhancement system 2 should not be interpreted to be limited to just these two configurations or embodiments.
- the ion transport system 6 is adjacent to the ion enhancement system 2 and may comprise a collecting capillary 5 or any ion optics, conduits or devices that may transport analyte ions and that are well known in the art.
- FIG. 2A shows a cross-sectional view of an AP-MALDI mass spectrometer system.
- the figure shows the system with a source housing 14.
- the use of the source housing 14 to enclose the ion source and system is optional. Certain parts, components and systems may or may not be under vacuum. These techniques and structures are well known in the art.
- the ion source 3 comprises a laser 4, a deflector 8 and a target support 10.
- a target 13 is applied to the target support 10 in a matrix material well known in the art.
- the laser 4 provides a laser beam that is deflected by the deflector 8 toward the target 13.
- the target 13 is then ionized and the analyte ions are released as an ion plume into an ionization region 15.
- the ionization region 15 is located between the ion source 3 and the collecting capillary 5.
- the ionization region 15 comprises the space and area located in the area between the ion source 3 and the collecting capillary 5.
- This region contains the ions produced by ionizing the sample that are vaporized into a gas phase.
- This region can be adjusted in size and shape depending upon how the ion source 3 is arranged relative to the collecting capillary 5.
- located in this region are the analyte ions produced by ionization of the target 13.
- the collecting capillary 5 is located downstream from the ion source 3 and may comprise a variety of material and designs that are well known in the art.
- the collecting capillary 5 is designed to receive and collect analyte ions produced from the ion source 3 that are discharged as an ion plume into the ionization region 15.
- the collecting capillary 5 has an aperture and/or elongated bore 12 that receives the analyte ions and transports them to another capillary or location.
- the collecting capillary 5 is connected to a main capillary 18 that is under vacuum and further downstream.
- the collecting capillary 5 may be supported in place by an optional insulator 17. Other structures and devices well known in the art may be used to support the collecting capillary 5.
- the conduit 9 provides a flow of heated gas toward the ions in the ionization region 15.
- the heated gas interacts with the analyte ions in the ionization region 15 to enhance the analyte ions and allow them to be more easily detected by the detector 11 (not shown in FIG. 2 ).
- These ions include the ions that exist in the heated gas phase.
- the detector 11 is located further downstream in the mass spectrometer (see FIG. 1 ).
- the conduit 9 may comprise a variety of materials and devices well known in the art.
- the conduit 9 may comprise a sleeve, transport device, dispenser, nozzle, hose, pipe, pipette, port, connector, tube, coupling, container, housing, structure or apparatus that is used to direct a heated gas or gas flow toward a defined region in space or location such as the ionization region 15. It is important to the invention that conduit 9 be positioned sufficiently close to the target 13 and the target support 10 so that a sufficient amount of heated gas can be applied to the ions in the ionization region 15.
- the gas source 7 provides the heated gas to the conduit 9.
- the gas source 7 may comprise any number of devices to provide heated gas. Gas sources are well known in the art and are described elsewhere.
- the gas source 7 may be a separate component as shown in FIGS 2-3 or may be integrated with a coupling 23 (shown in FIG. 4 ) that operatively joins the collecting capillary 5, the conduit 9 and the main capillary 18.
- the gas source 7, may provide a number of gases to the conduit 9.
- gases such as nitrogen, argon, xenon, carbon dioxide, air, helium etc.. may be used with the present invention.
- the gas need not be inert and should be capable of carrying a sufficient quantity of energy or heat.
- Other gases well known in the art that contain these characteristic properties may also be used with the present invention.
- FIG. 2B shows an embodiment of the invention.
- This embodiment includes the use of a heating device 16 that supplies heat to the target support 10.
- the heating device 16 is used with the conduit 9 and associated parts.
- the heating device 16 is used with the capillary 5 and serves the dual purpose of ion production and enhancement. Ion enhancement is obtained by applying heat to the ionization region 15.
- the heating device 16 supplies heat to the target support 10.
- the heat then enhances the ions in the ionization region 15 produced from ionization of the target 13.
- the heating device 16 also provide for the ionization of the target 13.
- Any heating device known in the art may be used to supply heat to the target support 10.
- Such heating devices may include and are not limited to conductive and radiative heating devices, an embedded heater, a heated fluid, a hot plate and a heated holder.
- FIG. 3A shows a cross sectional view of a further mass spectrometers system.
- the conduit 9 may be oriented in any number of positions to direct gas toward the ionization region 15.
- FIG. 3 in particular shows the conduit 9 in detached mode from the collecting capillary 5. It is important to the invention that the conduit 9 be capable of directing a sufficient flow of heated gas to provide enhancement to the analyte ions located in the ionization region 15.
- the conduit 9 can be positioned from around 1- 5 mm in distance from the target 13 or the target support 10.
- the heated gas applied to the target 13 and the target support 10 should be in the temperature range of about 60-150 degrees Celsius.
- the gas flow rate should be approximately 2-15 L/minute.
- FIG. 3B shows another embodiment of the invention.
- This embodiment includes the use of the heating device 16 that supplies heat to the target support 10.
- the heating device 16 is used with the conduit 9 and associated parts.
- the heating device 16 is used with the capillary 5 and serves the dual purpose of ion production and enhancement. Ion enhancement is obtained by applying heat to the ionization region 15.
- the heating device 16 supplies heat to the target support 10.
- the heat then enhances the ions in the ionization region 15 produced from ionization of the target 13.
- the heating device 16 also provide for the ionization of the target 13.
- FIGS. 4-6 show coupling 23 and its design for joining the collecting capillary 5, the main capillary 18, and the conduit 9.
- the coupling 23 is designed for attaching to a fixed support 31 (shown in FIGS. 7 and 8 ).
- the coupling 23 comprises a spacer 33, a housing 35, and a capillary cap 34 (See FIG. 5 ).
- the capillary cap 34 and the spacer 33 are designed to fit within the housing 35.
- the spacer 33 is designed to apply pressure to the capillary cap 34 so that a tight seal is maintained between the capillary cap 34 and the main capillary 18.
- the capillary cap 34 is designed to receive the main capillary 18.
- a small gap 36 is defined between the spacer 33 and the capillary cap 34 (See FIG. 6 ). The small gap 36 allows gas to flow from the gas source 7 into the collecting capillary 5 as opposed to out of the housing 35 as is accomplished with prior art devices.
- An optional centering device 40 may be provided between the collecting capillary 5 and the conduit 9.
- the centering device 40 may comprise a variety of shapes and sizes. It is important that the centering device 40 regulate the flow of gas that is directed into the ionization region 15, FIGS. 4-6 show the centering device as a triangular plastic insert. However, other designs and devices may be employed between the conduit 9 and the collecting capillary 5.
- FIG. 7 shows a cross sectional view of a prior art device.
- the collecting capillary 5 is connected to the main capillary 18 by the capillary cap 34.
- the capillary cap is designed for receiving the main capillary 18 and is disposed in the housing 35.
- the housing 35 connects directly to the fixed support 31.
- the gas source 7 provides the gas through the channels 38 defined between the housing 35 and the capillary cap 34. The gas flows from the gas source 7 into the channel 38 through a passageway 24 and then into an ionization chamber 30. The gas is released into the ionization chamber 30 and serves no purpose at this point.
- FIG. 8 shows a cross sectional view of a mass spectrometer system with the conduit 9 positioned between the ion source 3 and the gas source 7.
- the conduit 9 operates to carry the heated gas from the gas source 7 to the collecting capillary end 20. Gas is produced by the gas source 7, directed through the channels 38 and the small gap 36. From there the gas is carried into an annular space 42 defined between the conduit 9 and the collecting capillary 5. The heated gas then contacts the optional centering device 40 (not shown in FIG. 8 ).
- the centering device 40 is disposed between the collecting capillary 5 and the conduit 9 and shaped in a way to regulate the flow of gas to the ionization region 15. Gas flows out of the conduit 9 into the ionization region 15 adjacent to the collecting capillary end 20.
- the analyte ions in the ionization region 15 are heated by the gas that is directed into this region.
- Analyte ions that are then enhanced are collected by the collecting capillary 5, carried to the main capillary 18 and then sent to the detector 11.
- the detection limits and signal quality improve dramatically. This result is quite unexpected. For instance, since no solvent is used with AP-MALDI and MALDI ion sources and mass spectrometers, desolvation and/or application of a gas would not be expected to be effective in enhancing ion detection in matrix based ion sources and mass spectrometers. However, it is believed that the invention operates by the fact that large ion clusters are broken down to produce bare analyte ions that are more easily detectable. In addition, the application of heat also helps with sample evaporation.
- FIG. 9 shows the results without the addition of heated gas to the target or ionization region. The figure does not show the existence of sharp peaks (ion enhancement) at the higher m/z ratios.
- FIG. 10 shows the results with the addition of the heated gas to the target in the ionization region.
- the figure shows the existence of the sharp peaks (ion enhancement) at the higher m/z ratios.
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Abstract
Description
- The invention relates generally to the field of mass spectrometry and more particularly toward a heated target support to provide enhanced analtye ions in an atmospheric pressure matrix assisted laser desorption/ionization (AP-MALDI mass spectrometer.
- Most complex biological and chemical targets require the application of complementary multidimensional analysis tools and methods to compensate for target and matrix interferences. Correct analysis and separation is important to obtain reliable quantitative and qualitative information about a target. In this regard, mass spectrometers have been used extensively as detectors for various separation methods. However, until recently most spectral methods provided fragmentation patterns that were too complicated for quick and efficient analysis. The introduction of atmospheric pressure ionization (API) and matrix assisted laser desorption ionization (MALDI) has improved results substantially. For instance, these methods provide significantly reduced fragmentation patterns and high sensitivity for analysis of a wide variety of volatile and non-volatile compounds. The techniques have also had success on a broad based level of compounds including peptides, proteins, carbohydrates, oligosaccharides, natural products, cationic drugs, organoarsenic compounds, cyclic glucans, taxol, taxol derivatives, metalloporphyrins, porphyrins, kerogens, cyclic siloxanes, aromatic polyester dendrimers, oligodeoxynucleotides, polyaromatic hydrocarbons, polymers and lipids.
- According to the MALDI method of ionization, the analyte and matrix in solution is applied to a probe or target substrate. As the solvent evaporates, the analyte and matrix co-precipitate out of solution to form a solid solution of the analyte in the matrix on the target substrate. The co-precipitate is then irradiated with a short laser pulse inducing the accumulation of a large amount of energy in the co-precipitate through electronic excitation or molecular vibration of the matrix molecules. The matrix dissipates the energy by desorption, carrying along the analyte into the gaseous phase. During this desorption process, ions are formed by charge transfer between the photo-excited matrix and analyte.
- Conventionally, the MALDI technique of ionization is performed using a time-of-flight analyzer, although other mass analyzers such as an ion trap, an ion cyclotron resonance mass spectrometer and quadrupole time-of-flight are also used. These analyzers, however, must operate under high vacuum, which among other things may limit the target throughput, reduce resolution, capture efficiency, and make testing targets more difficult and expensive to perform.
- To overcome the above-mentioned disadvantages in MALDI, a technique referred to as AP-MALDI has been developed. This technique employs the MALDI technique of ionization, but at atmospheric pressure. The MALDI and the AP-MALDI ionization techniques have much in common. For instance, both techniques are based on the process of pulsed laser beam desorption/ionization of a solid-state target material resulting in production of gas phase analyte molecular ions.
- AP-MALDI can provide detection of a molecular mass up to 106 Da from a target size in the attamole range. In addition, as large groups of proteins, peptides or other compounds are being processed and analyzed by these instruments, levels of sensitivity become increasingly important. Various structural and instrument changes have been made to MALDI mass spectrometers in an effort to improve sensitivity. Additions of parts and components, however, provides for increased instrument cost. In addition, attempts have been made to improve sensitivity by altering the analyte matrix mixed with the target. These additions and changes, however, have provided limited improvements in sensitivity with added cost. More recently, the qualitative and quantitative effects of heat on performance of AP-MALDI has been studied and assessed. In particular, it is believed that the performance of an unheated (room temperature) AP-MALDI source is quite poor due to the large and varying clusters produced in the analyte ions. These large clusters are formed and stabilized by collisions at atmospheric pressure. The results of different AP- MALDI matrixes to different levels of heat have been studied. In particular, studies have focused on heating the transfer capillary near the source. These studies show some limited improvement in overall instrument sensitivity. A drawback of this technique is that heating and thermal conductivity of the system is limited by the materials used in the capillary. Furthermore, sensitivity of the AP MALDI source has been limited by a number of factors including the geometry of the target as well as its position relative to the capillary, the laser beam energy density on the target surface, and the general flow dynamics of the system.
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US 4,968,885 A discloses methods and apparatus for liquid sample introduction into chemical detectors that require the sample to be transformed from a flowing stream into either gaseous or particulate states. The effluent from either a process stream or a liquid chromatograph is nebulized by combined thermal and penumatic processes within an inner fused silicon capillary tube heated by conduction through a relatively conductive sheathing gas from a surrounding electrical resistance heated outer capillary tube composed of a pure metal having a comparatively high linear relationship between temperature and electrical resistance to provide a uniform conduction of heat energy to the inner tube to form a well-collimated, partially or completely desolvated aerosol, with the less volatile solute components of the sample stream remaining in the particulate state. - Laiko et. al., "atmospheric Pressure MALDI/Ion Trap Mass Spectrometry" in ANAL. CHEM. vol. 72, no. 21, 01 November 2000, pages 5239 - 5243, describe the coupling of a sample ionization technique, atmospheric pressure matrix-assisted laser desorption/ionization (AP MALDI) with an ion trap mass spectrometer.
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WO 00/77822 A2 -
US 6,140,639 A describes a system and a method for on-line coupling of liquid capillary separation with matrix-assisted laser desorption ionization mass spectrometric analysis. Analyte from liquid capillary separation is mixed with matrix molecules for matrix-assisted laser desorption ionization. Continuous flow of the analyte/matrix combined with vacuum conditions allows evaporation and crystallization of homogeneous samples on a solid sample surface. Dual use of laser irradiation to desorb/ionize and remove excess sample facilitates on-line use and automation. -
EP 0 964 427 A2 -
WO 03/073461 A1 - It is an object of the invention to improve the sensitivity and results of AP-MALDI mass spectrometers for increased and efficient ion enhancement.
- This object is achieved by a mass spectrometer according to
claim 1. - The invention is described in detail below with reference to the following figures:
-
FIG. 1A shows general block diagram of a mass spectrometer. -
FIG. 1B shows a second general block diagram of a mass spectrometer. -
FIG. 2A shows a first example of a mass spectrometer system. -
FIG. 2B shows an embodiment of the invention -
FIG. 3A shows a second example of a mass spectrometer system. -
FIG. 3B shows another embodiment of the invention -
FIG. 4 shows a perspective view of a conduit of a mass spectrometer system enclosing a collecting capillary of the mass spectrometer system. -
FIG. 5 shows an exploded view ofFig 4 . -
FIG. 6 shows a cross sectional view ofFig 4 . -
FIG. 7 shows a cross sectional view of a prior art device. -
FIG. 8 shows a cross sectional view of a conduit similar toFig. 6 . -
FIG. 9 shows the analysis results of a femto molar peptide mixture without heat supplied by the present invention. -
FIG. 10 shows analysis results of a femto molar peptide mixture with the addition of heat supplied by the present invention to the analyte ions produced by the ion source in the ionization region adjacent to the collecting capillary. - Before describing the invention in detail, it must be noted that, as used in this specification and the appended claims, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to "a conduit" includes more than one "conduit". Reference to a "matrix" includes more than one "matrix" or a mixture of "matrixes". In describing and claiming the present invention, the following terminology will be used in accordance with the definitions set out below.
- The term "adjacent" means, near, next to or adjoining. Something adjacent may also be in contact with another component, surround the other component, be spaced from the other component or contain a portion of the other component. For instance, a capillary that is adjacent to a conduit may be spaced next to the conduit, may contact the conduit, may surround or be surrounded by the conduit, may contain the conduit or be contained by the conduit, may adjoin the conduit or may be near the conduit.
- The term "conduit" or "heated conduit" refers to any sleeve, transport device, dispenser, nozzle, hose, pipe, plate, pipette, port, connector, tube, coupling, container, housing, structure or apparatus that may be used to direct a heated gas or gas flow toward a defined region in space such as an ionization region. In particular, the "conduit" may be designed to enclose a capillary or portion of a capillary that receives analyte ions from an ion source. The term should be interpreted broadly, however, to also include any device, or apparatus that may be oriented toward the ionization region and which can provide a heated gas flow toward or into ions in the gas phase and/or in the ionization region. For instance, the term could also include a concave or convex plate with an aperture that directs a gas flow toward the ionization region.
- The term "enhance" refers to any external physical stimulus such as heat, energy, light, or temperature change, etc.. that makes a substance more easily characterized or identified. For example, a heated gas may be applied to "enhance" ions. The ions increase their kinetic energy, potentials or motions and are declustered or vaporized. Ions in this state are more easily detected by a mass analyzer. It should be noted that when the ions are "enhanced", the number of ions detected is enhanced since a higher number of analyte ions are sampled through a collecting capillary and carried to a mass analyzer or detector.
- The term "ion source" or "source" refers to any source that produces analyte ions. Ion sources may include other sources besides AP-MALDI ion sources such as electron impact (herein after referred to as EI), chemical ionization (CI) and other ion sources known in the art. The term "ion source" refers to the laser, target substrate, and target to be ionized on the target substrate. The target substrate in AP-MALDI may include a grid for target deposition. Spacing between targets on such grids is around 1-10 mm. Approximately 0.5 to 2 microliters is deposited on each site on the grid.
- The term "ionization region" refers to the area between the ion source and the collecting capillary. In particular, the term refers to the analyte ions produced by the ion source that reside in that region and which have not yet been channeled into the collecting capillary. This term should be interpreted broadly to include ions in, on, about or around the target support as well as ions in the heated gas phase above and around the target support and collecting capillary. The ionization region in AP MALDI is around 1-5 mm in distance from the ion source (target substrate) to a collecting capillary (or a volume of 1-5 mm3). The distance from the target substrate to the conduit is important to allow ample gas to flow from the conduit toward the target and target substrate. For instance, if the conduit is too close to the target or target substrate, then arcing takes place when voltage is applied. If the distance is too far, then there is no efficient ion collection.
- The term "ion enhancement system" refers to any device, apparatus or components used to enhance analyte ions. The term does not include directly heating a capillary to provide conductive heat to an ion stream. For example, an "ion enhancement system" comprises a conduit and a gas source. An ion enhancement system may also include other devices well known in the art such as a laser, infrared red device, ultraviolet source or other similar type devices that may apply heat or energy to ions released into the ionization region or in the gas phase.
- The term "ion production and enhancement system" refers to any device, apparatus or components used to produce and enhance analyte ions. For instance, a heated target support can be used to both provide for ion production and enhancement. The term does not include directly heating a capillary to provide conductive heat to an ion stream. The ion production and enhancement system may further comprise an ion source and an ion enhancement system. The ion source and the ion enhancement system can be separate devices or integrated, part of or comprise the same apparatus.
- The term "ion transport system" refers to any device, apparatus, machine, component, capillary, that shall aid in the transport, movement, or distribution of analyte ions from one position to another. The term is broad based to include ion optics, skimmers, capillaries, conducting elements and conduits.
- The terms "matrix based", or "matrix based ion source" refers to an ion source or mass spectrometer that does not require the use of a drying gas, curtain gas, or desolvation step. For instance, some systems require the use of such gases to remove solvent or cosolvent that is mixed with the analyte. These systems often use volatile liquids to help form smaller droplets. The above term applies to both nonvolatile liquids and solid materials in which the sample is dissolved. The term includes the use of a cosolvent. Cosolvents may be volatile or nonvolatile, but must not render the final matrix material capable of evaporating in vacuum. Such materials would include, and not be limited to m-nitrobenzyl alcohol (NBA), glycerol, triethanolamine (TEA), 2,4-dipentylphenol,1,5-dithiothrietol/dierythritol (magic bullet), 2-nitrophenyl octyl ether (NPOE), thioglycerol, nicotinic acid, cinnamic acid, 2,5-dihydroxy benzoic acid (DHB), 3,5-dimethoxy-4-hydroxycinnamic acid (sinpinic acid), α-cyano-4-hydroxycinnamic acid (CCA), 3-methoxy-4-hydroxycinnamic acid (ferulic acid),), monothioglycerol, carbowax, 2-(4-hydroxyphenylazo)benzoic acid (HABA), 3,4-dihydroxycinnamic acid (caffeic acid), 2-amino-4-methyl-5-nitropyridine with their cosolvents and derivatives. In particular the term refers to MALDI, AP-MALDI, fast atom/ion bombardment (FAB) and other similar systems that do not require a volatile solvent and may be operated abode, at, and below atmospheric pressure.
- The term "gas flow", "gas", or "directed gas" refers to any gas that is directed in a defined direction in a mass spectrometer. The term should be construed broadly to include monatomic, diatomic, triatomic and polyatomic molecules that can be passed or blown through a conduit. The term should also be construed broadly to include mixtures, impure mixtures, or contaminants. The term includes both inert and non-inert matter. Common gases used with the present invention could include and not be limited to ammonia, carbon dioxide, helium, fluorine, argon, xenon, nitrogen, air etc..
- The term "gas source" refers to any apparatus, machine, conduit, or device that produces a desired gas or gas flow. Gas sources often produce regulated gas flow, but this is not required.
- The term "capillary" or "collecting capillary" shall be synonymous and will conform with the common definition(s) in the art. The term should be construed broadly to include any device, apparatus, orifice, tube, hose or conduit that may receive ions.
- The term "detector" refers to any device, apparatus, machine, component, or system that can detect an ion. Detectors may or may not include hardware and software. In a mass spectrometer the common detector includes and/or is coupled to a mass analyzer.
- The invention is described with reference to the figures. The figures are not to scale, and in particular, certain dimensions may be exaggerated for clarity of presentation.
-
FIG. 1A shows a general block diagram of a mass spectrometer. The block diagram is not to scale and is drawn in a general format because the present invention may be used with a variety of different types of mass spectrometers. Themass spectrometer 1 of the present invention comprises an ion production andenhancement system 37, anion transport system 6 and adetector 11. The ion production andenhancement system 37 may comprise anion source 3 andion enhancement system 2 as one integrated part (SeeFIG. 1A ) or as separate components (SeeFIG. 1B ). Theion source 3 may be located in a number of positions or locations. In addition, a variety of ion sources may be used with the present invention. For instance, EI, CI or other ion sources well known in the art may be used with the invention. In one embodiment of the present invention (FIG. 1B and2A ), theion enhancement system 2 may comprise aconduit 9 and a gas source 7. Theion enhancement system 2 should not be interpreted to be limited to just these two configurations or embodiments. Theion transport system 6 is adjacent to theion enhancement system 2 and may also comprise a collectingcapillary 5 or any ion optics, conduits or devices that may transport analyte ions and that are well known in the art. -
FIG. 1B shows a second general block diagram of a mass spectrometer. The block diagram is not to scale and is drawn in a general format, because the present invention may be used with a variety of different types of mass spectrometers. Themass spectrometer 1 of the present invention comprises theion source 3, theion enhancement system 2, theion transport system 6 and thedetector 11. Theion enhancement system 2 may be interposed between theion source 3 and theion detector 11 or may comprise part of theion source 3 and/or part of theion transport system 6. - As described above, the
ion source 3 may be located in a number of positions or locations. In addition, a variety of ion sources may be used with the present invention. For instance, EI, CI or other ion sources well known in the art may be used with the invention. Theion enhancement system 2 may comprise aconduit 9 and a gas source 7. Further details of theion enhancement system 2 are provided inFIGS 2-3 . Theion enhancement system 2 should not be interpreted to be limited to just these two configurations or embodiments. Theion transport system 6 is adjacent to theion enhancement system 2 and may comprise a collectingcapillary 5 or any ion optics, conduits or devices that may transport analyte ions and that are well known in the art. -
FIG. 2A shows a cross-sectional view of an AP-MALDI mass spectrometer system. For simplicity, the figure shows the system with asource housing 14. The use of thesource housing 14 to enclose the ion source and system is optional. Certain parts, components and systems may or may not be under vacuum. These techniques and structures are well known in the art. - The
ion source 3 comprises alaser 4, adeflector 8 and atarget support 10. Atarget 13 is applied to thetarget support 10 in a matrix material well known in the art. Thelaser 4 provides a laser beam that is deflected by thedeflector 8 toward thetarget 13. Thetarget 13 is then ionized and the analyte ions are released as an ion plume into anionization region 15. - The
ionization region 15 is located between theion source 3 and the collectingcapillary 5. Theionization region 15 comprises the space and area located in the area between theion source 3 and the collectingcapillary 5. This region contains the ions produced by ionizing the sample that are vaporized into a gas phase. This region can be adjusted in size and shape depending upon how theion source 3 is arranged relative to the collectingcapillary 5. Most importantly, located in this region are the analyte ions produced by ionization of thetarget 13. - The collecting
capillary 5 is located downstream from theion source 3 and may comprise a variety of material and designs that are well known in the art. The collectingcapillary 5 is designed to receive and collect analyte ions produced from theion source 3 that are discharged as an ion plume into theionization region 15. The collectingcapillary 5 has an aperture and/or elongated bore 12 that receives the analyte ions and transports them to another capillary or location. InFIG. 2 the collectingcapillary 5 is connected to amain capillary 18 that is under vacuum and further downstream. The collectingcapillary 5 may be supported in place by anoptional insulator 17. Other structures and devices well known in the art may be used to support the collectingcapillary 5. - Important to the invention is the
conduit 9. Theconduit 9 provides a flow of heated gas toward the ions in theionization region 15. The heated gas interacts with the analyte ions in theionization region 15 to enhance the analyte ions and allow them to be more easily detected by the detector 11 (not shown inFIG. 2 ). These ions include the ions that exist in the heated gas phase. Thedetector 11 is located further downstream in the mass spectrometer (seeFIG. 1 ). Theconduit 9 may comprise a variety of materials and devices well known in the art. For instance, theconduit 9 may comprise a sleeve, transport device, dispenser, nozzle, hose, pipe, pipette, port, connector, tube, coupling, container, housing, structure or apparatus that is used to direct a heated gas or gas flow toward a defined region in space or location such as theionization region 15. It is important to the invention thatconduit 9 be positioned sufficiently close to thetarget 13 and thetarget support 10 so that a sufficient amount of heated gas can be applied to the ions in theionization region 15. - The gas source 7 provides the heated gas to the
conduit 9. The gas source 7 may comprise any number of devices to provide heated gas. Gas sources are well known in the art and are described elsewhere. The gas source 7 may be a separate component as shown inFIGS 2-3 or may be integrated with a coupling 23 (shown inFIG. 4 ) that operatively joins the collectingcapillary 5, theconduit 9 and themain capillary 18. The gas source 7, may provide a number of gases to theconduit 9. For instance, gases such as nitrogen, argon, xenon, carbon dioxide, air, helium etc.. may be used with the present invention. The gas need not be inert and should be capable of carrying a sufficient quantity of energy or heat. Other gases well known in the art that contain these characteristic properties may also be used with the present invention. -
FIG. 2B shows an embodiment of the invention. This embodiment includes the use of aheating device 16 that supplies heat to thetarget support 10. Theheating device 16 is used with theconduit 9 and associated parts. In other words, theheating device 16 is used with thecapillary 5 and serves the dual purpose of ion production and enhancement. Ion enhancement is obtained by applying heat to theionization region 15. Theheating device 16 supplies heat to thetarget support 10. The heat then enhances the ions in theionization region 15 produced from ionization of thetarget 13. It is within the scope of the invention that theheating device 16 also provide for the ionization of thetarget 13. However, it is standard in the industry to use the laser 4 (as shown inFIGS. 2A-2B ,3A-3B ) to ionize such targets. Any heating device known in the art may be used to supply heat to thetarget support 10. Such heating devices may include and are not limited to conductive and radiative heating devices, an embedded heater, a heated fluid, a hot plate and a heated holder. -
FIG. 3A shows a cross sectional view of a further mass spectrometers system. Theconduit 9 may be oriented in any number of positions to direct gas toward theionization region 15.FIG. 3 in particular shows theconduit 9 in detached mode from the collectingcapillary 5. It is important to the invention that theconduit 9 be capable of directing a sufficient flow of heated gas to provide enhancement to the analyte ions located in theionization region 15. Theconduit 9 can be positioned from around 1- 5 mm in distance from thetarget 13 or thetarget support 10. The heated gas applied to thetarget 13 and thetarget support 10 should be in the temperature range of about 60-150 degrees Celsius. The gas flow rate should be approximately 2-15 L/minute. -
FIG. 3B shows another embodiment of the invention. This embodiment includes the use of theheating device 16 that supplies heat to thetarget support 10. Theheating device 16 is used with theconduit 9 and associated parts. In other words, theheating device 16 is used with thecapillary 5 and serves the dual purpose of ion production and enhancement. Ion enhancement is obtained by applying heat to theionization region 15. Theheating device 16 supplies heat to thetarget support 10. The heat then enhances the ions in theionization region 15 produced from ionization of thetarget 13. It is within the scope of the invention that theheating device 16 also provide for the ionization of thetarget 13. However, it is standard in the industry to use the laser 4 (as shown inFIGS. 2A-2B ,3A-3B ) to ionize such targets. Any heating device known in the art may be used to supply heat to thetarget support 10. -
FIGS 2 ,4-6 and8 illustrate that theconduit 9 is designed to enclose the collectingcapillary 5. Theconduit 9 may enclose all of the collectingcapillary 5 or a portion of it. However, it is important that theconduit 9 be adjacent to the collectingcapillary end 20 so that heated gas can be delivered to the analyte ions located in theionization region 15 before they enter or are collected by the collectingcapillary 5.
Theconduit 9 may be a separate component or may comprise a part of thecoupling 23.FIGS. 4-6 show theconduit 9 as a separate component. -
FIGS. 4-6 show coupling 23 and its design for joining the collectingcapillary 5, themain capillary 18, and theconduit 9. Thecoupling 23 is designed for attaching to a fixed support 31 (shown inFIGS. 7 and 8 ). Thecoupling 23 comprises aspacer 33, ahousing 35, and a capillary cap 34 (SeeFIG. 5 ). Thecapillary cap 34 and thespacer 33 are designed to fit within thehousing 35. Thespacer 33 is designed to apply pressure to thecapillary cap 34 so that a tight seal is maintained between thecapillary cap 34 and themain capillary 18. Thecapillary cap 34 is designed to receive themain capillary 18. Asmall gap 36 is defined between thespacer 33 and the capillary cap 34 (SeeFIG. 6 ). Thesmall gap 36 allows gas to flow from the gas source 7 into the collectingcapillary 5 as opposed to out of thehousing 35 as is accomplished with prior art devices. - An optional centering
device 40 may be provided between the collectingcapillary 5 and theconduit 9. The centeringdevice 40 may comprise a variety of shapes and sizes. It is important that the centeringdevice 40 regulate the flow of gas that is directed into theionization region 15,FIGS. 4-6 show the centering device as a triangular plastic insert. However, other designs and devices may be employed between theconduit 9 and the collectingcapillary 5. - Referring now to
FIGS. 1-8 , thedetector 11 is located downstream from theion source 3 and theconduit 9. Thedetector 11 may be a mass analyzer or other similar device well known in the art for detecting the enhanced analyte ions that were collected by the collectingcapillary 5 and transported to themain capillary 18. Thedetector 11 may also comprise any computer hardware and software that are well known in the art and which may help in detecting enhanced analyte ions. - Having described the invention and components in some detail, a description of how the invention operates is in order.
-
FIG. 7 shows a cross sectional view of a prior art device. The collectingcapillary 5 is connected to themain capillary 18 by thecapillary cap 34. The capillary cap is designed for receiving themain capillary 18 and is disposed in thehousing 35. Thehousing 35 connects directly to the fixedsupport 31. Note that the gas source 7 provides the gas through thechannels 38 defined between thehousing 35 and thecapillary cap 34. The gas flows from the gas source 7 into thechannel 38 through apassageway 24 and then into anionization chamber 30. The gas is released into theionization chamber 30 and serves no purpose at this point. -
FIG. 8 shows a cross sectional view of a mass spectrometer system with theconduit 9 positioned between theion source 3 and the gas source 7. Theconduit 9 operates to carry the heated gas from the gas source 7 to the collectingcapillary end 20.
Gas is produced by the gas source 7, directed through thechannels 38 and thesmall gap 36. From there the gas is carried into anannular space 42 defined between theconduit 9 and the collectingcapillary 5. The heated gas then contacts the optional centering device 40 (not shown inFIG. 8 ). The centeringdevice 40 is disposed between the collectingcapillary 5 and theconduit 9 and shaped in a way to regulate the flow of gas to theionization region 15. Gas flows out of theconduit 9 into theionization region 15 adjacent to the collectingcapillary end 20. The analyte ions in theionization region 15 are heated by the gas that is directed into this region. Analyte ions that are then enhanced are collected by the collectingcapillary 5, carried to themain capillary 18 and then sent to thedetector 11. It should be noted that after heat has been added to the analyte ions adjacent to the source, the detection limits and signal quality improve dramatically. This result is quite unexpected. For instance, since no solvent is used with AP-MALDI and MALDI ion sources and mass spectrometers, desolvation and/or application of a gas would not be expected to be effective in enhancing ion detection in matrix based ion sources and mass spectrometers. However, it is believed that the invention operates by the fact that large ion clusters are broken down to produce bare analyte ions that are more easily detectable. In addition, the application of heat also helps with sample evaporation. - It is to be understood that while the invention has been described in conjunction with the specific embodiments thereof, that the foregoing description as well as the examples that follow are intended to illustrate and not limit the scope of the invention. Other aspects, advantages and modifications within the scope of the invention will be apparent to those skilled in the art to which the invention pertains.
- A Bruker Esquire-LC ion trap mass spectrometer was used for AP-MALDI studies. The mass spectrometer ion optics were modified (one skimmer, dual octapole guide with partitioning) and the ion sampling inlet of the instrument consisted of an ion sampling capillary extension with a conduit concentric to a capillary extension. The ion sampling inlet received a gas flow of 4-10 L/min. of heated nitrogen. A laser beam (337.1 nm, at 10 Hz) was delivered by a 400 micron fiber through a single focusing lens onto the target. The laser power was estimated to be around 50 to 70 uJ. The data was obtained by using Ion Charge Control by setting the maximum trapping time to 300 ms (3 laser shots) for the mass spectrometer scan spectrum. Each spectrum was an average of 8 micro scans for 400 to 2200 AMU. The matrix used was an 8 mM alpha-cyano-4-hydroxy-cinnamic acid in 25% methanol, 12% TPA, 67% water with 1% acetic acid. Matrix targets were premixed and 0.5 ul of the matrix/target mixture was applied onto a gold plated stainless steel target. Targets used included trypsin digest of bovine serum albumin and standard peptide mixture containing angiotensin I and II, bradykinin, and fibrinopeptide A. Temperature of the gas phase in the vicinity of the target (ionization region) was 25 degrees Celsius.
FIG. 9 shows the results without the addition of heated gas to the target or ionization region. The figure does not show the existence of sharp peaks (ion enhancement) at the higher m/z ratios. - The same targets were prepared and used as described above except that heated gas was applied to the target (ionization region) at around 100 degrees Celsius.
FIG. 10 shows the results with the addition of the heated gas to the target in the ionization region. The figure shows the existence of the sharp peaks (ion enhancement) at the higher m/z ratios.
Claims (5)
- A mass spectrometer (1) that produces analyte ions for ease of detection by a detector (11), comprising:(a) a matrix assisted laser desorption ionisation (MALDI) ion source (3) for producing analyte ions wherein the MALDI ion source (3) comprises
a target support (10) configured to have applied on a first side thereof a target (13)
a laser (4) configured to provide a laser beam to the target (13) applied onto the target support (10) and
a heating device (16) mounted to the target support (10) and the heating device being configured to provide heat to the target support (10) to enhance analyte ions in an ionization region (15);(b) a collecting capillary (5) downstream from said MALDI ion source (3) for receiving said analyte ions produced from said MALDI ion source (3), wherein said ionization region (15) is located between the target support (10) of the MALDI ion source (3) and said collecting capillary (5);(c) a detector (11) downstream from said collecting capillary (5) for detecting said analyte ions received by said collecting capillary (5);(d) a gas source for providing a gas, wherein said gas provided by said gas source is heated; and(e) a conduit (9) for directing a flow of said heated gas from said gas source to said ionitation region (15). - The mass spectrometer as recited in claim 1, wherein said MALDI ion source (3) is at about atmospheric pressure.
- The mass spectrometer as recited in claim 1, wherein said MALDI ion source (3) is above atmospheric pressure.
- The mass spectrometer as recited in claim 1, wherein said MALDI ion source (3) is below atmospheric pressure.
- The mass spectrometer as recited in claim 1 wherein said detector (11) comprises a mass analyzer.
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PCT/US2003/002527 WO2003094206A2 (en) | 2002-04-29 | 2003-01-28 | Target support and method for ion production enhancement |
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WO2003073461A1 (en) * | 2002-02-22 | 2003-09-04 | Agilent Technologies, Inc. | Apparatus and method for ion production enhancement |
Also Published As
Publication number | Publication date |
---|---|
EP1500124A4 (en) | 2007-11-07 |
WO2003094206A2 (en) | 2003-11-13 |
US20050098722A1 (en) | 2005-05-12 |
WO2003094206A3 (en) | 2004-02-05 |
EP1500124A2 (en) | 2005-01-26 |
DE60336897D1 (en) | 2011-06-09 |
US6858841B2 (en) | 2005-02-22 |
US20030160167A1 (en) | 2003-08-28 |
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